Connectivity and function of inhibitory neurons in the primate visual cortex

灵长类视觉皮层抑制性神经元的连接和功能

• 批准号: 10745862
• 负责人: Alessandra Angelucci
• 金额: $ 9.69万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745862
• 关键词: Academia; Address; Administrative Supplement; Anatomy; Anions; Area; Award; Brain; Callithrix; Cells; Cerebral cortex; Collaborations; Communities; Defect; Development; Epilepsy; Foundations; Functional disorder; Funding; Gene Expression; Genes; Glycoproteins; Goals; Knowledge; Left; Measures; Mental disorders; Monkeys; Mus; Neurologic; Neurons; Opsin; Outsourcing; Parents; Parvalbumins; Plasmids; Positioning Attribute; Primates; Privatization; Production; Rabies virus; Regulatory Element; Schizophrenia; Serotyping; Somatostatin; Specificity; Stroke; Testing; Tva receptor; Variant; Viral Vector; Virus; Vision; Visual Cortex; Washington; Work; adeno-associated viral vector; anatomical tracing; austin; brain dysfunction; cost; experimental study; inhibitory neuron; insight; interest; nervous system disorder; neuronal cell body; nonhuman primate; novel strategies; rabies virus glycoprotein G; vector

SUMMARY The goals and specific aims of the present Administrative Supplement application are unchanged with respect to the parent R01 award. Here we request additional funds for unanticipated expenses within the original scope of the project. In the original application we proposed to use viral vectors that specifically infect somatostatin (SOM) and parvalbumin (PV) inhibitory neurons in non-human primate cortex. These viral vectors were generated and provided by our collaborators Dr Zemelman at UT Austin (a subcontract PI in the first two years of the project), Dr Dimidschstein (Broad Institute), and Dr Horwitz (Univ. of Washington). In the first two years of the project, we tested and validated the 3 types of PV-specific viruses generated by our collaborators. Dr Dimidschstein’s virus showed the highest specificity for PV neurons. Unfortunately, however, Dr Dimidschstein has recently left academia and is no longer in a position to provide us with this vector and its variants at no cost. We have, therefore, started a collaboration with Drs Gordon Fishell (Harvard) and Dr. Gabrielle Pouchelon (Cold Spring Harbor) to generate variants of the Dimidschstein PV-specific virus that express the necessary genes to perform the TRIO experiments proposed in Aim 1 of the project, to trace anatomical inputs to PV cells. Moreover, we are working with private companies (Genewiz and Addgene) and the U Penn Viral Vector Core to generate variants of this PV-specific virus carrying the genes for excitatory and inhibitory opsins; these are necessary to address Aim 3 of the project. These new approaches require significant additional expenses which we cannot cover with the funds awarded. The requested cost increases would allow us to address part of Aim1 and Aim3 of the project using vectors with >90% specificity as validated by our studies performed in the initial years of the project. We will make accessible to the community the vectors generated with the additional funds.

概括 目前行政补充申请的目标和具体目的没有变化 关于母公司 R01 奖励，我们在此请求额外资金以应对意外情况。 在原来的项目范围内我们建议使用。 特异性感染生长抑素（SOM）和小白蛋白（PV）抑制性神经元的病毒载体 在非人类灵长类动物皮层中，这些病毒载体是由我们生成和提供的。 合作者：德克萨斯大学奥斯汀分校的 Zemelman 博士（该项目前两年的分包 PI）、 Dimidschstein（博德研究所）和 Horwitz 博士（华盛顿大学）在项目的头两年。 项目中，我们测试并验证了我们的合作者生成的 3 种 PV 特异性病毒。 然而不幸的是，Dimidschstein 博士的病毒对 PV 神经元表现出最高的特异性。 Dimidschstein 博士最近离开了学术界，无法再为我们提供这一信息 因此，我们开始与戈登博士合作。 Fishell（哈佛大学）和 Gabrielle Pouchelon 博士（冷泉港）生成了 Dimidschstein PV 特异性病毒，表达执行 TRIO 所需的基因 该项目目标 1 中提出的实验旨在追踪光伏电池的解剖输入。 我们正在与私营公司（Genewiz 和 Addgene）以及宾夕法尼亚大学病毒载体核心合作 生成携带兴奋性和抑制性基因的这种 PV 特异性病毒的变体 视蛋白；这些对于实现该项目的目标 3 是必要的。 我们无法用所授予的资金支付的大量额外费用。 成本增加将使我们能够使用向量来解决该项目的部分目标 1 和目标 3 经过我们在项目最初几年进行的研究验证，特异性 >90%。 向社区提供用额外资金产生的载体。